Division of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201 002, India.
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi 576104, Karnataka, India.
Life Sci. 2023 Oct 1;330:122027. doi: 10.1016/j.lfs.2023.122027. Epub 2023 Aug 18.
Acute lung inflammation, particularly acute respiratory distress syndrome (ARDS), is caused by a variety of pathogens including bacteria and viruses. β-Glucans have been reported to possess both anti-inflammatory and immunomodulatory properties. The current study evaluated the therapeutic effect of β-glucans on polyinosinic:polycytidylic acid (Poly(I:C)) induced lung inflammation in both hamster and mice models.
Poly(I:C)-induced ALI/inflammation models were developed in hamsters (2.5 mg/kg) and mice (2 mg/kg) by delivering the Poly(I:C) intratracheally, and followed with and without β-glucan administration. After treatment, lung mechanics were assessed and lung tissues were isolated and analyzed for mRNA/protein expression, and histopathological examinations.
Poly(I:C) administration, caused a significant elevation of inflammatory marker's expression in lung tissues and showed abnormal lung mechanics in mice and hamsters. Interestingly, treatment with β-glucan significantly (p < 0.001) reversed the Poly(I:C)-induced inflammatory events and inflammatory markers expression in both mRNA (IL-6, IL-1β, TNF-α, CCL2 and CCL7) and protein levels (TNF-α, CD68, myeloperoxidase, neutrophil elastase, MUC-5Ac and iNOS). Lung functional assays revealed that β-glucan treatment significantly improved lung mechanics. Histopathological analysis showed that β-glucan treatment significantly attenuated the Poly(I:C) induced inflammatory cell infiltration, injury and goblet cell population in lung tissues. Consistent with these findings, β-glucan treatment markedly reduced the number of neutrophils and macrophages in lung tissues. Our findings further demonstrated that β-glucan could reduce inflammation by suppressing the MAPK pathway.
These results suggested that β-glucan may attenuate the pathogenic effects of Poly(I:C)-induced ALI/ARDS via modulating the MAPK pathway, indicating β-glucan as a possible therapeutic agent for the treatment of viral-pulmonary inflammation/injury.
急性肺炎症，特别是急性呼吸窘迫综合征（ARDS），由多种病原体引起，包括细菌和病毒。β-葡聚糖具有抗炎和免疫调节特性。本研究评估了β-葡聚糖对聚肌苷酸：聚胞苷酸（Poly（I：C））诱导的仓鼠和小鼠模型中肺炎症的治疗作用。
通过气管内递送 Poly（I：C），在仓鼠（2.5mg/kg）和小鼠（2mg/kg）中建立 Poly（I：C）诱导的 ALI/炎症模型，并在给予和不给予β-葡聚糖后进行治疗。治疗后，评估肺力学，并分离和分析肺组织的 mRNA/蛋白表达和组织病理学检查。
Poly（I：C）给药导致肺组织中炎症标志物的表达显著升高，并导致小鼠和仓鼠的肺力学异常。有趣的是，β-葡聚糖治疗显著（p<0.001）逆转了 Poly（I：C）诱导的炎症事件和 mRNA（IL-6、IL-1β、TNF-α、CCL2 和 CCL7）和蛋白水平（TNF-α、CD68、髓过氧化物酶、中性粒细胞弹性蛋白酶、MUC-5Ac 和 iNOS）的炎症标志物表达。肺功能测定显示，β-葡聚糖治疗显著改善了肺力学。组织病理学分析表明，β-葡聚糖治疗显著减轻了 Poly（I：C）诱导的肺组织炎症细胞浸润、损伤和杯状细胞数量。与这些发现一致，β-葡聚糖治疗显著减少了肺组织中的中性粒细胞和巨噬细胞数量。我们的研究结果进一步表明，β-葡聚糖可以通过抑制 MAPK 通路来减轻炎症。
这些结果表明，β-葡聚糖可能通过调节 MAPK 通路减轻 Poly（I：C）诱导的 ALI/ARDS 的发病作用，表明β-葡聚糖可能是治疗病毒性肺炎症/损伤的一种潜在治疗剂。
